Classification attempt of breast cancer by gene analysis system

Research Project

Project/Area Number	18K15225
Research Category	Grant-in-Aid for Early-Career Scientists
Allocation Type	Multi-year Fund
Review Section	Basic Section 50010:Tumor biology-related
Research Institution	Aichi Medical University
Principal Investigator	Ido Mirai 愛知医科大学, 医学部, 助教 (70740968)
Project Period (FY)	2018-04-01 – 2022-03-31
Project Status	Completed (Fiscal Year 2021)
Budget Amount *help	¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000) Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	トリプルネガティブ乳癌 / FAM64A / 網羅的遺伝子解析 / 網羅的遺伝子検索 / 乳癌 / トリプルネガティブ / 免疫組織染色
Outline of Final Research Achievements	We investigated the clinicopathological characteristics of FAM64A protein, which has been implicated in the development of breast cancer. In immunostaining of surgical specimens, FAM64A-positive cases expressed the protein in the nucleus and correlated with triple negative (hormone negative, HER2 negative), high histological grade, and high Ki67index. FAM64A was found to cause cell death in FAM64A-positive breast cancer cell lines by knockdown analyses, and to bind to proteins involved in DNA stabilization and drug resistance. It is a potential therapeutic target for breast cancer and is expected to be applied as a molecular marker for breast cancer segmentation and treatment decision making.
Academic Significance and Societal Importance of the Research Achievements	FAM64Aは特にトリプルネガティブ乳癌（TNBC）の一群において、その細胞増殖に必修な核蛋白であった。さらにSMARCA5-BAZ1B複合体の先行研究を踏まえ、FAM64A陽性TNBCは陰性TNBCとは異なるDAN複製機序や抗がん剤耐性を示す可能性が示唆された。以上からFAM64Aは治療標的となり得ること、乳癌の細分化や治療方針決定の分子マーカーになる可能性が示めされ、乳癌の特に予後不良のTNBCに対する新たな情報の手がかりとなることが期待された。